Highlights
– FMT did not significantly enhance MDRO decolonization (31.0% vs 30.4% in sham group) or reduce AMR genes in GI disease patients.
– FMT enriched short-chain fatty acid-producing bacteria but induced only transient mycobiome changes.
– Viral diversity remained unchanged post-FMT.
– No significant difference in adverse events between FMT and sham groups.
Background
Gut colonization by multidrug-resistant organisms (MDROs) poses a significant risk for subsequent infections, particularly in patients with gastrointestinal diseases. Despite the growing threat of antimicrobial resistance (AMR), there are no approved therapeutic interventions for MDRO decolonization. Fecal microbiota transplant (FMT) has emerged as a potential strategy to restore gut microbiota and combat MDROs. This randomized clinical trial aimed to evaluate the efficacy of FMT in decolonizing MDROs and reducing AMR genes in patients with GI diseases.
Study Design
This was a randomized, double-blind, sham-controlled clinical trial conducted at a tertiary care center in India. Participants included 114 patients with GI diseases (mean age 40.6 years, 70.2% male) who had persistent MDRO colonization. Patients were randomized to receive either FMT via colonoscopy (n=58) or a sham intervention (sigmoidoscopy with saline injection, n=56). The co-primary outcomes were MDRO decolonization rate and decrease in AMR genes at 4 weeks post-intervention. Secondary outcomes included changes in gut microbiome, virome, and mycobiome composition, incidence of MDRO infections, and adverse events.
Key Findings
The intention-to-treat analysis revealed no significant differences in MDRO decolonization between the FMT and sham groups (31.0% vs 30.4%; absolute difference 0.6%, 95% CI -16.2% to 17.6%; P=0.94). Similarly, there was no significant reduction in AMR genes (median 2.5 genes in FMT group vs 2.0 in sham group; P=0.68).
Microbiome analysis showed enrichment of short-chain fatty acid-producing bacteria in the FMT group, but these changes did not correlate with clinical outcomes. Viral diversity remained unchanged, and mycobiome alterations were modest and transient. Adverse events were comparable between groups, indicating FMT was safe in this population.
Expert Commentary
The trial’s findings challenge the hypothesis that a single FMT session can effectively decolonize MDROs in GI disease patients. The lack of significant differences in primary outcomes suggests that more intensive or prolonged microbiota modulation strategies may be needed. The study’s rigorous design and blinded assessment strengthen its validity, but the single-center setting may limit generalizability. Future research should explore optimized FMT protocols or adjunct therapies to enhance decolonization efficacy.
Conclusion
While FMT modulated gut microbiome composition, it did not significantly decolonize MDROs or reduce AMR genes in this trial. These results highlight the complexity of MDRO colonization and the need for alternative strategies to combat antimicrobial resistance in high-risk GI populations.
Funding and Registration
Clinical Trials Registry-India Registration No. 2022/07/043847.
References
Narang H, et al. Fecal Microbiota Transplant and Multidrug-Resistant Organism Decolonization in Gastrointestinal Disease: A Randomized Clinical Trial. JAMA Intern Med. 2026; PMID: 42008253.